Knee OA is a leading cause of chronic disability in older Americans. Few strategies to prevent knee OA development, progression, or disability exist, due to limited knowledge of the responsible factors. There has been increasing recognition of the role of knee laxity and malalignment, two potentially modifiable factors that are the focus of the current application. These factors are being examined in the ongoing 300-subject MAK study (Mechanical Factors in Arthritis of the Knee) at Northwestern University, in which extensive experience has been gained with them, and evidence of their importance has accumulated. [unreadable] [unreadable] Now proposed is a comprehensive examination of the effect of laxity and malalignment in subjects with or at high risk to develop knee OA, as an ancillary study to the recently funded Multicenter OA Study (MOST). MOST is a study of 3000 men and women, with the primary goal of examining the effect of a panel of risk factors on OA outcomes over 3 years. MOST involves 4 sites: the Coordinating and MRI Reading Center (UCSF), Data Analysis and X-ray Reading Center (BU), and 2 Clinical Centers (UAB and UI). [unreadable] [unreadable] Hypotheses of this application focus on whether laxity and malalignment are each associated with: a higher risk of incident OA than non-lax knees and more neutrally aligned knees; a decline in physical function; risk of OA progression. Primary hypotheses focus on symptom and x-ray outcomes; MRI-based assessment of cartilage morphology is also proposed as a means of examining the compartment-specific effects of each of these factors in a subset of the MOST cohort. [unreadable] [unreadable] Support is requested: to replicate in MOST the measurement systems and protocols (for laxity and alignment) currently in use in the MAK study; to assess laxity and alignment at the baseline exam of MOST; in a subset of the cohort, to obtain MRI at baseline and at 3 year follow-up using a high-field scanner to examine change in cartilage volume and thickness as outcomes of laxity and malalignment; and to test the relationship of laxity and malalignment with risk of important OA outcomes.